Regulation of blood flow, capillary function and metabolic rate are closely coupled in striated muscle, however the pathways which couple arteriolar responses specifically to exercise remain elusive. Very little is known about how changes in metabolism are coupled to capillary recruitment (i.e. to changes in blood flow distribution). Our studies provide a direct link between muscle contraction and conducted vasodilations in the arterioles that control capillary recruitment and hence flow distribution. The proposed studies will be undertaken in cremaster muscles of anesthetized Golden hamsters, using local stimulation of groups of muscle fibers underlying only capillaries, and observing remote arteriolar responses upstream. Three hypotheses will be tested. Hypothesis I: In response to contraction of muscle fibers underlying only the capillaries, remote dilation of the inflow arteriole to the capillary module, and the branch and transverse arterioles upstream, is mediated by a signal that is transmitted along the vessel wall. This will be explored by locally blocking gap junction signals, and by comparing the signal transfuction mechanisms with those of other conducted responses. Hypothesis II: Dilation of arterioles upstream from the module inflow vessel during remote muscle fiber contraction is dependent on flow or pressure changes in the module inflow arteriole. IIA. The arteriolar response to remote muscle fiber contraction is modulated by changes in flow (or pressure). The role of hemodynamic changes in initiating or modulating the remote response will be tested. Hypothesis III. The initiating signal for the communication pathway that results in remote upstream arteriolar dilation involves changed adenosine metabolism or changed PO2. IIIA. KATP channel activity is necessary for the arteriolar response to remote muscle contraction. We will ask if the response is initiated by mediators commonly implicated in exercise hyperemia. These studies will establish the pathway which directly couples local muscle activity to capillary blood flow, and will lay the groundwork for studies aimed at identifying the elusive molecule(s) responsible for communication between striated muscle fibers and the microvasculature i.e., for mediating a basic mechanism of exercise hyperemia. Understanding the cardiovascular mechanisms underlying exercise is relevant to many areas of human health; this proposal will contribute new information about the pathways that specifically couple muscle fiber contraction to dilation of those arterioles that control capillary blood flow distribution.

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National Heart, Lung, and Blood Institute (NHLBI)
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Experimental Cardiovascular Sciences Study Section (ECS)
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University of Rochester
Schools of Dentistry
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Duza, Tasmia; Sarelius, Ingrid H (2004) Increase in endothelial cell Ca(2+) in response to mouse cremaster muscle contraction. J Physiol 555:459-69
Murrant, C L; Duza, T; Kim, M B et al. (2004) Arteriolar dilations induced by contraction of hamster cremaster muscle are dependent on changes in endothelial cell calcium. Acta Physiol Scand 180:231-8
Duza, Tasmia; Sarelius, Ingrid H (2004) Localized transient increases in endothelial cell Ca2+ in arterioles in situ: implications for coordination of vascular function. Am J Physiol Heart Circ Physiol 286:H2322-31
Duza, Tasmia; Sarelius, Ingrid H (2003) Conducted dilations initiated by purines in arterioles are endothelium dependent and require endothelial Ca2+. Am J Physiol Heart Circ Physiol 285:H26-37
Cohen, Kenneth D; Sarelius, Ingrid H (2002) Muscle contraction under capillaries in hamster muscle induces arteriolar dilatation via K(ATP) channels and nitric oxide. J Physiol 539:547-55
Murrant, Coral L; Sarelius, Ingrid H (2002) Multiple dilator pathways in skeletal muscle contraction-induced arteriolar dilations. Am J Physiol Regul Integr Comp Physiol 282:R969-78
Sarelius, I H; Cohen, K D; Murrant, C L (2000) Role for capillaries in coupling blood flow with metabolism. Clin Exp Pharmacol Physiol 27:826-9
Murrant, C L; Sarelius, I H (2000) Local and remote arteriolar dilations initiated by skeletal muscle contraction. Am J Physiol Heart Circ Physiol 279:H2285-94
Cohen, K D; Berg, B R; Sarelius, I H (2000) Remote arteriolar dilations in response to muscle contraction under capillaries. Am J Physiol Heart Circ Physiol 278:H1916-23
Murrant, C L; Sarelius, I H (2000) Coupling of muscle metabolism and muscle blood flow in capillary units during contraction. Acta Physiol Scand 168:531-41

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